This SBIR FAST-TRACK application is designed to address the urgent problem of prescription drug abuse (PDA) among adolescents in the U.S. There is a dearth of primary prevention programs for PDA that have demonstrated changes in behavior as part of a rigorously designed evaluation. Research shows that a substantial number of youth who misuse prescription drugs initiate use during their teen years and that the age of onset of PDA is decreasing. While there are a number of drug abuse prevention programs for middle school age youth, relatively few programs focus on preventing PDA. Furthermore, due to growing constraints on classroom time, new evidence-based prevention programs are needed that flexibly incorporate the use of online digital technology and classroom/small-group components. Because alcohol, tobacco, and other drug (ATOD) abuse typically co- occur with PDA and share similar risk and protective factors, prevention programs for PDA should address ATOD and incorporate best practices in effective substance abuse prevention. To meet the need for an effective primary prevention approach to the problem of PDA in middle school youth, we propose to develop and test an adaptation of the evidence-based substance abuse and violence prevention approach called Life Skills Training (LST). The LST program has been extensively tested and found to effectively prevent substance abuse, violence and aggression in a series of randomized controlled trials with behavioral effects reported in over 30 peer-reviewed publications. The proposed preventive intervention for middle school PDA will (1) utilize both online digital and face-to-face intervention modalities to address PDA and concurrent ATOD use; (2) positively change social norms and challenge positive expectancies regarding PDA and ATOD use; (3) discourage diversion of prescription medications; (4) enhance protective factors by building social and self-regulation skills through interactive learning and behavioral rehearsal scenarios; and (5) incorporate online booster sessions. In Phase I, we will focus group test the materials with middle school students, teachers, and academic administrators to demonstrate feasibility, relevance, usability, and appeal. Materials will be revised based on focus group feedback, and then we will conduct a rigorous national randomized trial of the prevention program in Phase II. Middle schools (N=36) will be randomized into either an intervention group that will receive the new intervention or a treatment-as-usual control group that will receive existing health education programming. At the end of the intervention period, and at 6- and 12-month follow-up assessments, we will compare both groups with respect to changes in behaviors, norms, attitudes, and knowledge regarding PDA and ATOD use. This research offers the potential to identify an innovative, effective, interactive, and engaging preventive intervention that utilizes both online digital technology and small-group/classroom methods and that can reduce PDA, be widely disseminated, and, ultimately, decrease the adverse consequences of PDA and ATOD use.